The goal of the study was to explore trends since quitting smoking, and the risk of bladder cancer, among postmenopausal women who were former smokers.

Questions Addressed:

What was the dose-response relationship between years since quitting smoking (YSQ) and the risk of bladder cancer among postmenopausal women who were former smokers?

Did associations differ among bladder cancer subtypes?

Did the risk among former smokers ever normalize to the risk faced by those who never smoked?

Action Points

Former smokers saw a 25% decline in their bladder cancer risk within the first 10 years of cessation, and that risk continued to decrease as cessation time increased, but remained higher than never smokers after 30 years of quitting.

Note that this study highlights the importance of primary prevention and the importance of smoking cessation.

Synopsis and Perspective:

Results from a longitudinal study of >160,000 women (ages 50 to 79) in the Women's Health Initiative (WHI) demonstrated a significant reduction in the risk of bladder cancer after quitting smoking.

Traces of blood in the urine for a woman are typically associated with menstruation or menopause. Depending on age or other factors recorded during clinical work-up, an initial diagnosis could be made of postmenopausal bleeding, cystitis, or a urinary tract infection. As a result, bladder cancer may be overlooked in women, as the disease is associated with age and is more prevalent in men.

Bu bladder cancer is the sixth most common cancer in the U.S., can occur at any age, and tends to be more aggressive in women (greater muscle invasion rate), suggesting that estrogen inhibits tumor initiation, but promotes invasion. While all the reasons are not fully understood, previous studies have suggested that postmenopausal women may have a higher risk of bladder cancer compared with women who have not undergone menopause.

Generally speaking, smoking is the most important risk factor for bladder cancer, with estimates suggesting that about half of bladder cancers can be attributed to combustible tobacco use. Early age at menopause (age <45) is also associated with an increased risk for bladder cancer and this risk is magnified in female smokers.

Among WHI participants who quit cigarettes, bladder cancer risk declined by 25% within the first 10 years of quitting, then continued to decline at a slower rate after that, reported Yueyao Li, MSPH, MD, a PhD candidate at the Indiana University in Bloomington, and colleagues in Cancer Prevention Research.

Compared with postmenopausal women who had never smoked cigarettes, current smokers had a roughly four-fold increased risk for developing bladder cancer, while the risk among postmenopausal former smokers who quit smoking 3 decades earlier or more was roughly half that, Li said.

"Obviously, the best way to prevent bladder cancer is to never start smoking in the first place, but our findings show that, even among older women, quitting can make a big difference in risk," Li told MedPage Today.

The researchers examined data from 143,279 women, all of whom had provided information about current smoking status and smoking histories. More than half (52.7%) of the women were "never smokers," 40.2% were former smokers, and 7.1% were current smokers. Baseline features that set former smokers apart from never smokers were the fact that they tended to be slightly younger, were more likely to be non-Hispanic whites, tended to have lower BMIs, were more likely to hold higher educational degrees, were more likely to work in managerial or professional fields, to be divorced or separated, to have higher rates of cancer in their family histories, to be current drinkers, and to have low fat dietary intake.

Over an average of 14.8 years of follow-up, the researchers identified 870 bladder cancer cases. Compared with never smokers, former smokers had twice the risk of bladder cancer, and current smokers had more than three times the risk.

Cox proportional hazards regression models were used to estimate age- and multivariable-adjusted (for variables such as education, race/ethnicity, BMI, and dietary factors) hazard ratios (HRs) and their 95% confidence intervals.

The steepest reduction was observed after the first 10 years of quitting, but even after 30 years, the risk remained higher than for never smokers (HR 1.92, 95% CI 1.43-2.58). But when compared with women who continued to smoke, women who quit smoking during follow-ups had a 39% reduction in bladder cancer risk (HR 0.61, 95% CI 0.40-0.94), and this risk continued to decline over time.

There was no significant difference in smoking cessation and HR of bladder cancer across different subtypes.

The researchers cautioned that, because of the small numbers of cases for subtypes of bladder cancer, they were restricted in terms of their analysis of associations between smoking cessation and risks of other subtypes of bladder cancer. However, they argued that their results still had public health significance, as papillary and transitional cell carcinomas comprise 90% to 95% of all bladder cancers.

Li and colleagues also stated that the generalizability of their findings could be attenuated because the prevalence of smoking was less among WHI participants (6.9%) than among the entire U.S. population (15.1%).

Using a large, prospective cohort study of postmenopausal women, the researchers showed that former smokers versus current smokers experienced a 25% decrease in risk of bladder cancer within 10 YSQ, and this risk continued to decline over time.

While the relationship between smoking and risk of bladder cancer has been well-established by previous studies conducted in both genders, the magnitude of this risk reduction among former smokers was controversial, they wrote. Prior studies conducted in the general population also yielded inconsistent results with respect to whether the risk of bladder cancer for former smokers could decrease to the level of never smokers. Bladder cancer risk decreased to the level of never smokers after 20 years of smoking cessation, based on some studies. However, other studies found that bladder cancer risk decreased as YSQ increased, but the risk remained elevated after quitting smoking for >20 years, according to Li and colleagues.

After adjusting for numbers of cigarettes per day or pack years of smoking, current results showed that the risk of bladder cancer in former smokers remained significantly higher than that of never smokers, even after >30 YSQ. Thus, smoking intensity and duration should be taken into account when analyzing the smoking-bladder cancer connection.

Associations among smoking initiation age, duration of smoking, and risks for bladder cancer were stronger in invasive subtypes in comparison with noninvasive subtypes, based on evidence from the literature. Smoking cessation was linked to a reduction in all types of bladder cancer, with the magnitude of the drop being greater in superficial than invasive malignancies.

While the biological mechanisms of the association between bladder cancer and smoking are not known, the study illustrated an additional health benefit from smoking cessation.

Last Updated June 21, 2019

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

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